Pathogen-selective killing by guanylate-binding proteins as a molecular mechanism leading to inflammasome signaling.

Feng, S; Enosi Tuipulotu, D; Pandey, A; Jing, W; Shen, C; Ngo, C; Tessema, MB; Li, F-J; Fox, D; Mathur, A; Zhao, A; Wang, R; Pfeffer, K; Degrandi, D; Yamamoto, M; Reading, PC; Burgio, G; Man, SM

Pathogen-selective killing by guanylate-binding proteins as a molecular mechanism leading to inflammasome signaling.

Feng, S Enosi Tuipulotu, D

Pandey, A Jing, W Shen, C Ngo, C Tessema, MB Li, F-J Fox, D Mathur, A Zhao, A Wang, R Pfeffer, K Degrandi, D Yamamoto, M Reading, PC Burgio, G Man, SM

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Publisher:: NATURE PORTFOLIO
Publication Type:: Journal Article
Citation:: Nat Commun, 2022, 13, (1), pp. 4395
Issue Date:: 2022-07-29

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Field	Value	Language
dc.contributor.author	Feng, S
dc.contributor.author	Enosi Tuipulotu, D https://orcid.org/0000-0002-6442-4633
dc.contributor.author	Pandey, A
dc.contributor.author	Jing, W
dc.contributor.author	Shen, C
dc.contributor.author	Ngo, C
dc.contributor.author	Tessema, MB
dc.contributor.author	Li, F-J
dc.contributor.author	Fox, D
dc.contributor.author	Mathur, A
dc.contributor.author	Zhao, A
dc.contributor.author	Wang, R
dc.contributor.author	Pfeffer, K
dc.contributor.author	Degrandi, D
dc.contributor.author	Yamamoto, M
dc.contributor.author	Reading, PC
dc.contributor.author	Burgio, G
dc.contributor.author	Man, SM
dc.date.accessioned	2025-01-15T13:32:00Z
dc.date.available	2022-07-18
dc.date.available	2025-01-15T13:32:00Z
dc.date.issued	2022-07-29
dc.identifier.citation	Nat Commun, 2022, 13, (1), pp. 4395
dc.identifier.issn	2041-1723
dc.identifier.issn	2041-1723
dc.identifier.uri	http://hdl.handle.net/10453/183653
dc.description.abstract	Inflammasomes are cytosolic signaling complexes capable of sensing microbial ligands to trigger inflammation and cell death responses. Here, we show that guanylate-binding proteins (GBPs) mediate pathogen-selective inflammasome activation. We show that mouse GBP1 and GBP3 are specifically required for inflammasome activation during infection with the cytosolic bacterium Francisella novicida. We show that the selectivity of mouse GBP1 and GBP3 derives from a region within the N-terminal domain containing charged and hydrophobic amino acids, which binds to and facilitates direct killing of F. novicida and Neisseria meningitidis, but not other bacteria or mammalian cells. This pathogen-selective recognition by this region of mouse GBP1 and GBP3 leads to pathogen membrane rupture and release of intracellular content for inflammasome sensing. Our results imply that GBPs discriminate between pathogens, confer activation of innate immunity, and provide a host-inspired roadmap for the design of synthetic antimicrobial peptides that may be of use against emerging and re-emerging pathogens.
dc.format	Electronic
dc.language	eng
dc.publisher	NATURE PORTFOLIO
dc.relation.ispartof	Nat Commun
dc.relation.isbasedon	10.1038/s41467-022-32127-0
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Animals
dc.subject.mesh	Bacteria
dc.subject.mesh	Carrier Proteins
dc.subject.mesh	Cytosol
dc.subject.mesh	GTP-Binding Proteins
dc.subject.mesh	Immunity, Innate
dc.subject.mesh	Inflammasomes
dc.subject.mesh	Mammals
dc.subject.mesh	Mice
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Cytosol
dc.subject.mesh	Animals
dc.subject.mesh	Mammals
dc.subject.mesh	Mice
dc.subject.mesh	Bacteria
dc.subject.mesh	GTP-Binding Proteins
dc.subject.mesh	Carrier Proteins
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Immunity, Innate
dc.subject.mesh	Inflammasomes
dc.subject.mesh	Animals
dc.subject.mesh	Bacteria
dc.subject.mesh	Carrier Proteins
dc.subject.mesh	Cytosol
dc.subject.mesh	GTP-Binding Proteins
dc.subject.mesh	Immunity, Innate
dc.subject.mesh	Inflammasomes
dc.subject.mesh	Mammals
dc.subject.mesh	Mice
dc.subject.mesh	Signal Transduction
dc.title	Pathogen-selective killing by guanylate-binding proteins as a molecular mechanism leading to inflammasome signaling.
dc.type	Journal Article
utslib.citation.volume	13
utslib.location.activity	England
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2025-01-15T13:31:57Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	13
utslib.citation.issue	1

Abstract:

Inflammasomes are cytosolic signaling complexes capable of sensing microbial ligands to trigger inflammation and cell death responses. Here, we show that guanylate-binding proteins (GBPs) mediate pathogen-selective inflammasome activation. We show that mouse GBP1 and GBP3 are specifically required for inflammasome activation during infection with the cytosolic bacterium Francisella novicida. We show that the selectivity of mouse GBP1 and GBP3 derives from a region within the N-terminal domain containing charged and hydrophobic amino acids, which binds to and facilitates direct killing of F. novicida and Neisseria meningitidis, but not other bacteria or mammalian cells. This pathogen-selective recognition by this region of mouse GBP1 and GBP3 leads to pathogen membrane rupture and release of intracellular content for inflammasome sensing. Our results imply that GBPs discriminate between pathogens, confer activation of innate immunity, and provide a host-inspired roadmap for the design of synthetic antimicrobial peptides that may be of use against emerging and re-emerging pathogens.

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http://hdl.handle.net/10453/183653